Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China.
Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China.
Biomed Pharmacother. 2020 Jun;126:110095. doi: 10.1016/j.biopha.2020.110095. Epub 2020 Mar 24.
We previously demonstrated that collagen metabolism affects scleral mechanical properties and scleral remodeling. Scleral remodeling changes the mechanical strain on sclera and scleral fibroblasts. We postulated that mechanical strain changes affect collagen metabolism in scleral fibroblasts. To understand the differences in collagen metabolism in scleral fibroblasts related to mechanical strain changes, scleral fibroblasts were isolated and cultured under different mechanical strains using the FX-4000 system or were treated with the TGF-β1 and TGFBR1 inhibitor LY364947. The collagen metabolism-related gene expression levels were detected. The results showed that the appropriate (lower) mechanical strain improved collagen synthesis and reduced collagen decomposition. In contrast, higher mechanical strain reduced collagen synthesis and enhanced collagen decomposition, especially a sustained higher strain. Furthermore, the effect of a transitory higher strain was recoverable, and collagen metabolism in scleral fibroblasts was regulated by TGF-β1. These results suggested that mechanical strain mediates TGF-β1 expression to regulate collagen metabolism in scleral fibroblasts, thereby affect scleral tissue remodeling.
我们之前的研究表明，胶原代谢会影响巩膜的力学性能和重塑。巩膜重塑会改变巩膜和巩膜成纤维细胞的机械应变。我们推测，机械应变的改变会影响巩膜成纤维细胞中的胶原代谢。为了了解与机械应变改变相关的巩膜成纤维细胞中胶原代谢的差异，我们使用 FX-4000 系统分离并培养了巩膜成纤维细胞，并施加不同的机械应变，或用 TGF-β1 和 TGFBR1 抑制剂 LY364947 处理。检测了胶原代谢相关基因的表达水平。结果表明，适当（较低）的机械应变可促进胶原合成，减少胶原分解。相反，较高的机械应变会减少胶原合成并增强胶原分解，尤其是持续的高应变。此外，短暂的高应变的效果是可恢复的，并且巩膜成纤维细胞中的胶原代谢受 TGF-β1 调节。这些结果表明，机械应变通过调节 TGF-β1 的表达来介导巩膜成纤维细胞中的胶原代谢，从而影响巩膜组织重塑。
